A phase 2 study of seribantumab (MM-121) in combination with docetaxel or pemetrexed versus docetaxel or pemetrexed alone in patients with heregulin positive (HRG+), locally advanced or metastatic non-small cell lung cancer (NSCLC).
Bibliographic record
Abstract
TPS9110 Background: The role of the HER3 receptor and its ligand heregulin (HRG) in the progression of multiple cancers has been well established. Seribantumab (MM-121) is a fully human, monoclonal IgG2 antibody that binds to the HRG domain of HER3, blocking HER3 activity. In retrospective analyses of prior seribantumab Phase 2 studies, high levels of HRG mRNA appeared to predict poor outcome when patients received standard of care (SOC) treatment. Addition of seribantumab to SOC improved progression-free survival (PFS) in patients with HRG positive (HRG+) tumors, consistent with the hypothesis that blockade of HRG-induced HER3 signaling by seribantumab can restore sensitivity to SOC impacted by HRG. Methods: In the current randomized, open-label, international, Phase 2 study, NSCLC patients will be screened for HRG using an RNA in situ hybridization assay on a recent biopsy tissue sample. Approximately 560 patients will be screened to support enrollment of 280 HRG+ patients, who will be randomized in a 2:1 ratio to receive seribantumab plus investigator’s choice of docetaxel or pemetrexed, or docetaxel or pemetrexed alone. Patients will be wild-type for EGFR and ALK and will have progressed following one to three systemic therapies for locally advanced and/or metastatic disease, including one platinum-containing regimen and anti-PD-1/PD-L1 where available and clinically indicated. The primary endpoint is overall survival (OS). Secondary endpoints include PFS, objective response rate and time to progression. The study has > 80% power to detect a 33% risk improvement in median OS (hazard ratio ≤ 0.67), using a one-sided, stratified log-rank test at a significance level of 0.025. An interim analysis is planned when 50% of final OS events have been reported. Enrollment was initiated in June 2015. Approximately 80 sites worldwide will be open to enrollment by the end of 2016. Clinical trial information: NCT02387216.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".